Surgical results and quality of life of patients submitted to restorative proctocolectomy and ileal pouch-anal anastomosis

ABSTRACT Purpose: restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice in some cases of familial adenomatous polyposis (FAP) and ulcerative colitis (UC). IPAA allows complete removal of the diseased colon and rectum, however, it is associated with substantial morbidity and potential consequences to patients’ quality of life (QoL). Aims: to evaluate the surgical results, functional outcomes and QoL after IPAA; and to examine the impact of surgical complications upon QoL. Methods: we reviewed the records of 55 patients after IPAA, with emphasis on surgical outcomes. Forty patients answered the questionnaires. The Cleveland Global Quality of Life (CGQL), Inflammatory Bowel Disease Questionnaire (IBDQ), and Short Form 36 Health Survey Questionnaire (SF36). Results: the average age was 42.1±14.1 years. 63.6% of the patients were male, and 69.1% had FAP. Operative mortality was 1.8% and overall morbidity was 76.4%. Anastomotic leakage was the most frequent early complication (34.5%). Pouchitis (10.8%) and small bowel obstruction (9.1%) were the most common late complications. Patients with UC had the most severe complications (p=0.014). Pelvic complications did not have a negative effect on functional outcomes or QoL scores. Female patients had decreased pouch evacuation frequency, fewer nocturnal bowel movements, decreased bowel symptom impact on QoL (p=0.012), and better CGQL (p=0.04). Patients with better education had better QoL scores, and patients who had their pouches for more than five years scored lower. Conclusion: the high morbidity has no impact on function or QoL. Bowel function is generally acceptable. QoL is good and affected by sex, education and time interval since IPAA.


METHODS
This is a cross-sectional, descriptive, and analytical study, in which we evaluated 67 patients with a diagnosis of UC or FAP who underwent PCT with J-shaped IPAA by the Coloproctology group at the Alfa Institute of Gastroenterology, Hospital das Clinicas, UFMG, from January 2003 to April 2017.We performed no sample calculation, considering all patients in that period who met the study's inclusion and exclusion criteria.
We included patients over 18 years, who underwent PCT-IPAA, agreed to participate in the study, and signed an informed consent form.
We excluded patients with a presumed diagnosis of UC who later developed criteria for Crohn's disease diagnosis, who were illiterate or unable to understand the terms of the study, those with incapacitating physical condition impairment, and patients with incomplete medical records.
For the assessment of pouchitis episodes, we excluded ileostomized patients (six individuals with definitive ileostomies due to IPAA failure and two with protective ileostomies) and one who died due to complications of ileostomy closure.
For the evaluation of IPAA function and QoL, we excluded ileostomized patients, the deceased, and those patients with less than a year of stoma closure.
After applying the inclusion and exclusion criteria, we included 55 patients for the analysis of surgical outcomes, 46 individuals for the evaluation of pouchitis, and 40 for QoL evaluation (Figure 1).
We collected data on socio-demographics, surgery indication, presence or absence of malignancy in the surgical specimen, surgical strategy (one, two or three steps), anastomosis type (stapled or manual), and surgical outcomes, including complications.
The operations were performed in one, two or three steps, depending on patients' indication and clinical status.When performed in two stages, the first procedure consisted of the PCT-IPAA and a protective ileostomy, and in the second stage, the ileostomy was closed.In the three-stage surgery, the pelvic part of the surgery was performed after improvement of the patient's clinical condition.Therefore, the first stage comprised subtotal colectomy with terminal ileostomy and mucous fistula of the sigmoid remnant; the second stage comprehended the protectomy with IPAA and protective ileostomy; and the closure of the ileostomy in the third stage.We considered early complications those that occurred within 30 days of any of the surgical procedures, and the late ones, those that occurred after that period.We classified early complications according to the Clavien-Dindo surgical complications score 13 .
We considered an anastomotic fistula to be any defect in intestinal integrity at the anastomosis site leading to communication between the intra and extraintestinal compartments.According to this classification, we also considered abscesses at the same site as the anastomosis to be fistulas 14 , analyzing them together.
Pelvic complications were the ones related to the proctectomy and the manufacturing of the IPAA, thus comprising the following: anastomotic stenosis, IPAA fistula to the vagina, pelvic abscess or anastomotic fistula, pelvic hemorrhage, stapling line bleeding, lesion of the distal ureter, and IPAA fistula to the bladder.
We classified IPAA failure as the need for permanent stoma, with or without IPAA excision 15 .
For the other described complications, we considered the clinical suspicion as duly registered in the medical records and the results of complementary exams, when requested.
Surgical death was that which occurred at any time during the surgical procedure and within 30 days afterwards.
The time of IPAA was calculated between the time elapsed from the closing date of the ileostomy and the date of the interview to assess QoL.
We assessed QoL with 40 patients through face-to-face application of the Short Form Health Survey (SF36) 16 , the Inflammatory Bowel Disease Questionnaire (IBDQ) 17 , the Cleveland Global Quality of Life (CGQL) 18 , and questions specific to the IPAA function.
We also inquired patients specifically about the IPAA function, assessing urgency, incontinence, fecal leak, number of bowel movements in 24 hours and at night, food restriction, incomplete bowel movements, and the use of antidiarrheal medications.These questions, as well as the subjective question ("how do intestinal symptoms affect your quality of life") were adapted from specific functional questionnaires [19][20][21] .As these questionnaires were not validated for Brazil, the calculation of the scores was not performed, only the description of results.

This study was approved by the Ethics in
Research Committee of UFMG (COEP) -Project CAAE 50917215000005149.

Statistical analysis
We computed the mean ± standard deviation (SD) for quantitative variables when their distribution was normal, and median (Q1;Q3) for non-normallydistributed variables.We described categorical variables with absolute frequency and percentage.For comparison between categorical variables, we performed the exact and asymptotic Chi-square Pearson tests.
For comparisons of the quantitative variables, if the variable was not normally distribution, we used the Mann Whitney and Kruskal Wallis tests.In the multiple comparison paired test after a significant Kruskal Wallis test, we used the Mann Whitney test with Bonferrone correction.The normal distribution test used was the Shapiro Wilk.In the analysis of correlations, we used the Spearman test.
The level of significance used was 0.05 and the software used was the Statistical Package for Social Sciences (SPSS).

RESULTS
Of the 55 patients included, the majority were male (63.6%), with a mean age of 42.1 ± 14.1 years, and most (55.1%) had more than eight years of schooling.
Most patients had FAP (69.1%) and 26% of these had concomitant colon adenocarcinoma.
The main indication for IPAA in UC was clinical treatment failure (76.5%), followed by severe acute colitis (17.6%), and dysplasia (one patient -5.9%).At the time of surgery indication, 94.1% of patients used corticosteroids, and 52.9%, anti TNF alpha drugs.
Regarding the surgical technique, most anastomoses were performed by double stapling (94.7%).
The three-step procedure was performed in 58.8% of cases of UC, the remainder of patients undergoing two-step surgery.In FAP cases, all approaches were performed in two stages, except for one patient (1.8%) in whom it was not possible to perform an ileostomy due to technical difficulties related to the great thickness of the abdominal wall and a short mesentery.Surgical morbidity was 76.4%, and mortality, 1.8%.Early complications occurred in 65.5% of patients, and late complications, in 41.8%.
The most frequent early complication was anastomotic fistula or pelvic abscess, in 19 patients (34.5%), with no statistically significant difference between patients with UC or FAP (Table 1).Two patients died, one who had FAP, of urothelial carcinoma of the bladder (non-surgical death), and the other with UC, who had fistula and fecal peritonitis after the closure of the protective ileostomy.
In the assessment of the QoL and IPAA function, 40 patients were included, 15 with UC and 25 with FAP.The mean age was 39.2 ± 13.1 years.Twentyfive patients were male (62.5%) and the IPAA time varied from one to 11 years, with a median of 3.75 years.
The obstetric history showed that eight women (53.3%) were nulliparous and four (26.7%) had previous vaginal deliveries, the maximum of vaginal deliveries being two.
In the assessment of IPAA function (n = 40), the median of evacuations in 24 hours was six, one at night.Most patients (87.5%) did not have incontinence for solid stools, while 50% reported fecal leak.
Evacuation urgency was reported by 32.5% of patients, with all patients maintaining fecal containment for more than half an hour.As for the feeling of incomplete evacuation, 20% reported more than four episodes a day.Antidiarrheal medication was used by 60%, while 76.3% referred food restriction.There was no statistical difference in IPAA function due to disease or to the presence or absence of pelvic complications.
In the assessment of QoL (n = 40), 65% said that the intestinal symptoms had little or no impact on their quality of life, and the average CGQL score was 0.82 and all SF36 domains had median above 70 points (Figure 2).
Neither the disease that led to surgery (FAP Female patients had less bowel movement, less impact of intestinal symptoms on quality of life, and better CGQL scores than men (Table 4).
Patients with higher education had better SF36 scores in the physical, pain, and general domains, although the assessment of specific IPAA function showed not statistical difference according to the level of education (Table 4).Regarding IPAA time, there was no significant difference as to intestinal function, while in QoL evaluation there was worsening in the SF36 general domain with increasing IPAA time (Figure 3).
was clinical intractability, which is in accordance with the literature [27][28][29] , but the use of corticosteroids (94.1%) was higher than in most series, where the rate is 70% 28 .
This, associated with the use of biological therapy and the impairment of the patients' general condition, justified the use of the three-step approach in most patients with UC, which was not observed in patients with FAP.
The diversion of intestinal transit by a protective ileostomy after making the IPAA does not seem to decrease or prevent the formation of IPAA fistulas 30 .On the other hand, it can reduce the clinical consequences of fistulas, which are often disastrous, such as pelvic sepsis 1 .Ileostomy, however, is not a morbidityfree procedure, with dehydration, hydroelectrolytic disorders, enteric fistula in the reconstruction of transit, and intestinal obstruction as some of the complications described 1 .
Although the occurrence of pelvic sepsis is higher in patients without a protective stoma, complications such as stenosis and IPAA failure tend to occur more in ileostomized patients 31 .However, there is a tendency to indicate the protective stoma for patients at increased risk, such as the elderly, male, in use of higher doses of corticosteroids, and with high body mass index 32 .When these conditions are not present, some centers tend not to perform the protective stoma, carrying out the modified, one or two-stage surgery 33,34 .
In the present study, the only case in which no protective ileostomy was performed due to technical difficulties presented a pelvic abscess, with the formation of an IPAA fistula for the vagina.In contrast, the only surgical death occurred due to a fistula in the ileoleal anastomosis after closure of the ileostomy The surgical mortality of IPAA is about 1% 15,18 , and our results (1.8%) are compatible with the literature.
The low mortality is justified by the presence of mostly young patients, operations performed in tertiary care center, by a specialized team, and preoperative selection of patients 15 .In our country, Leal et al. 3

DISCUSSION
The IPAA technique revolutionized the surgical treatment of patients with indication for PCT, by avoiding the definitive ileostomy while maintaining the natural evacuation route.It is, however, a surgical procedure with high morbidity, even when performed in reference centers.
In the present study, most patients had a diagnosis of FAP with prophylactic indication for the operation.This is incongruent with most international reference centers, in which 80% to 95% of the population is made up of patients with UC 18,[22][23][24][25][26] .
Being a reference center for more complex surgeries, HC-UFMG constantly receives many cases of FAP.In addition, because of the investigation of family members, the institution has a constant inflow of patients requiring the procedure due to this indication.It can also be speculated that such divergence results from possible resistance in the surgical indication in patients with UC in our environment, with greater insistence on maintaining different modalities of drug treatments in detriment to the surgical one.
The morbidity rates published in the literature are quite disparate, ranging from 19% to 62.5%, depending on the criteria used in various studies 15 .The morbidity observed in our study can be considered high, reaching 76.4%.Anastomotic fistula was the most common early complication, its rate of 34.5% being significantly higher than described in the literature.
These vary between 5% and 25% 1,3,15,24,25,30,35 .Such heterogeneity is justified in part by the different concepts of fistula, as well as by the experience of the surgical team and the profile of the operated patients.
In the present study, we considered the broader concept of fistula, regardless of radiological confirmation, with pelvic abscesses being added to the analysis, to increase diagnosis sensitivity.Some authors have observed higher rates of septic complications in patients with UC 36,37 , which is incongruent with our findings.There was no statistical difference in early complications as to disease type.However, patients with UC had more severe early complications according to the Clavien-Dindo classification, which is justified by the profile of patients with UC, who mostly presented active inflammation and were using immunosuppressive medication, mainly corticosteroids.
The second most frequent early complication was pelvic hemorrhage, with rates also higher than the literature, which range from 2.4% 38 to 8% 23 .
Despite the great early surgical morbidity, more than 64.4% of these complications were managed conservatively (Clavien-Dindo I and II), reaching 79.7%, also considering the approaches under local anesthesia, such as puncture guided by image (Clavien-Dindo I, II and IIIa).
The occurrence of pouchitis and intestinal obstruction were the most common late complications and the rates are in agreement with those reported in the literature 18,38 .Pouchitis consists of non-specific inflammation of the IPAA in the absence of intestinal diversion or complications 1 .Although the cause is still unknown, there is recent evidence that IPAA dysbiosis and abnormal mucosal immune response are implicated in the pathogenesis 39 .It presents with symptoms of tenesmus, increased number of bowel movements, fecal leaks, incontinence, urgency, as well as cramps and, occasionally, fever and anal bleeding 39,40 .The reports of pouchitis in FAP patients vary between 0 and 10% 3,41 , and in the UC these rates reach 40%, in 10 years of IPAA 1 , with an accumulated prevalence of up to 50% 39 , having an important impact on long-term QoL in patients with UC 42 .
With regard to anastomotic stenosis, we found a lower rate than in other studies, in which they vary from 6.8% 2 to 20% 43 .
The rate of IPAA fistula to other organs, such as the vagina, is in agreement with the ones of reference centers 15,25 , and there is evidence in the literature suggesting a progressive decrease of such complication with the service time experience 25 .
IPAA failure varies in the literature from 2.4% 38 , 6% 15 to 9% 44,45 , which is compatible with our results (9.1%).The main causes of IPAA failure is fistula to the vagina and other pelvic organs and the reservoir septic complications 46 , which are also in line with our findings.
Pelvic complications represent an important part of surgical morbidity, not only due to prevalence and severity, but also due to the potential worsening of IPAA function in the long term.The incidence of pelvic complications ranges from 12% 5 to 40.8% 47 .Some studies have assessed only the septic pelvic complications and others use a more comprehensive definition, as we did here.Pelvic complications, as well as their multiple approaches, could result in greater fibrosis and pelvic adhesions, with impairment of IPAA accommodativeness and function, and possible QoL deterioration 23 .Though we found a high rate of pelvic complications (47.3%), this did not influence the IPAA function or the QoL.
The literature is controversial when addressing the impact of pelvic complications on IPAA function and The assessment of QoL by IBDQ rendered a total score considered good and compatible with that reported by the literature 48 .In the evaluation by domains, the results were higher than the ones reported by the national literature 9 .Likewise, the values of SF36 by domains in this study were good and compatible with other publications 48,49 , with all domains scoring higher than 70.
In a recent publication, a Cleveland Clinic group evaluated the IPAA function and the QoL using clinical parameters and CGQL in 3,707 patients 24 .
QoL was excellent for patients with both UC and FAP, regardless of the time of IPAA, data compatible with the results of the present study.
As for the impact of intestinal symptoms on QoL, our results agree with most studies in the literature.
Patients have a high degree of satisfaction with the surgery and little impact on quality of life, as reported by most individuals 18,20,24,49,50 .
Specifically regarding the IPAA function, the occurrence of six bowel movements in 24 hours with only one at night can be considered quite satisfactory 24,25,48,51 .
In addition, most patients can delay bowel movements for more 30 minutes 48 and deny incontinence for solid stool 24,50 .As for the presence of fecal leak and incomplete evacuation, our data are also quite like those of other authors.Fecal leak is present in 40% to 50% of patients 24,25,48 , while in 25% 25 this escape is nocturnal, and approximately 60% of patients exhibit more than one episode of incomplete evacuation a day 48 .
Regarding the assessment of QoL and IPAA function, there was no difference between patients with UC or FAP, although we would expect a greater impact on QoL of patients with FAP, since such patients do not live with chronic symptoms related to the presence of intestinal inflammation, as usually occurs in those with UC.Other authors also did not observe any functional or QoL difference when analyzing patients with FAP or UC undergoing IPAA 18,52 .
Female patients admittedly have worse IPAA function, displaying more urgency and bowel movements in 24 hours 48 , increased nighttime frequency, and daytime incontinence 53 , in addition to worse QoL among those who became pregnant and delivered after the IPAA 42 .It is believed that there is an influence of other factors that justify these results, such as the number and route of delivery or the occurrence of obstetric injuries, although this has not yet been adequately evaluated in high-impact studies 48,54 .However, the present study found the opposite, with women presenting better CGQL scores, reports of lesser interference of intestinal symptoms with QoL, fewer nighttime and 24-hour bowel movements, and a tendency to report less food restriction.The selection of patients for IPAA may have strongly influenced these results, as in our sample most women were young, nulliparous or with up to two vaginal deliveries.Other factors, such as greater care with own health [55][56][57] and dietary habits 58,59 contribute to better functional results in females.Although education does not influence IPAA function, patients with a higher educational level showed better results in the evaluation by SF36 in the general, physical, and pain domains, in addition to a tendency for better results also in the functional and social domains.
Higher education implies not only better knowledge of the disease itself and the surgical procedure the patient has undergone, but also results in a greater financial return on work activities, an increased sense of personal control, and freedom of decision 52,60,61 .These factors contribute to a greater capacity for adaptation 52,61 after IPAA, which would result in fewer functional limitations.
We observed no functional changes related to the time elapsed after the IPAA, probably due to the small sample size.Such results are quite variable, mainly due to the different periods evaluated.Cleveland Clinic authors 18,24 demonstrated stable IPAA function even after ten years of follow-up.On the other hand, the opposite has been noted in studies with 20 or more years of follow up48, suggesting function deterioration, with increased nighttime frequency, fecal leaks, need for antidiarrheic medications, and use of hygienic protection 51 .In all of these studies 24,48,51 , despite function worsening, the QoL as measured by the CGQL and SF36 scores remained unchanged and at high levels over time.
Our results also show high, stable QoL, with worsening only in the overall SF36, with statistically significant difference between groups with one and two years of IPAA compared with those with more than five years.This result was not consistent with the literature and may have been influenced by the sample size or age and comorbidities in the group with longer IPAA time.

Surgical results and quality of life of patients submitted to restorative proctocolectomy and ileal pouch-anal anastomosis
This study presents limitations, the absence of sample calculation and sample size being the main ones, not allowing for more stratification of patients, and possibly interfering with the results statistical analysis.In addition, the evaluation of surgical results was performed by review of medical records, which may generate some bias in data collection and interpretation.

Figure 1 .
Figure 1.Flowchart of patient selection for outcome evaluation surgical, QoL and IPAA function.

Alves
Surgical results and quality of life of patients submitted to restorative proctocolectomy and ileal pouch-anal anastomosis or UC) nor the presence of pelvic complications had a statistically significant relationship with these results.Patients with UC also responded the IBDQ questionnaire, which showed good results, with median 180.When evaluating the median by domain, the intestinal one was 57.0 (54.0; 60.0), the systemic IBDQ was 28.0 (24.0; 30.0), the social IBDQ was 30.0 (27.0; 32.0), and the emotional, 65.0 (50.0; 73.0).

Figure 2 .
Figure 2. Evaluation of the results of the SF36 questionnaire by domains in patients undergoing PCT with IPAA.

Alves
Surgical results and quality of life of patients submitted to restorative proctocolectomy and ileal pouch-anal anastomosisYes, between half an hour and five min 0

Figure 3 .
Figure 3. Result of the comparison of the SF36 domains by IPAA time.
QoL.Recent work has shown an impact on the IBDQ scores in patients with early pelvic complications of Clavien-Dindo grades III and IV23 .On the other hand, reports state that patients with UC who underwent PCT-IPAA did not have their QoL or IPAA function affected by pelvic complications or by the multiple surgical interventions necessary to treat them5,7 .
Another limiting factor was the absence of cross cultural validation of the main IPAA function evaluation questionnaires in our midst.The three IPAA function questionnaires most used in the literature are the Function Oresland Score 21 , the Pouch Function Score 19 , and the Pouch Disfunction Score 20 .All questionnaires score the different complaints related to the IPAA and generate a result on a numerical scale.The higher the result, the worse the IPAA's function at all scales.In the absence of their cross cultural validation, there was an evaluation of all items separately, without generating numerical results, which would certainly facilitate the evaluation of the obtained data and the comparison with those published in the literature.On the other hand, it was possible to present a detailed survey of surgical, functional, and QoL results in patients undergoing IPAA, from a national sample, considering that this type of procedure is still relatively little performed in our country.Thus, we hope to contribute to the increase in the indication of this type of procedure, as well as to a better understanding of complications and correlation with the functional and QoL-related results.We expect that other national studies, preferably multi-institutional, may bring more robust results in terms of functional and QoL results, in addition to being able to validate the specific questionnaires of IPAA function, thus facilitating the postoperative monitoring of patients and the comparison with the international literature data.CONCLUSION PCT-IPAA has low mortality and high morbidity, the most serious early complications occurring more frequently in patients with UC.Despite this, the IPAA function and QoL can be considered satisfactory, regardless of the type of disease and the occurrence of pelvic complications.Female patients display better IPAA function and QoL.However, patients with higher education levels, despite having the same IPAA function, have better QoL scores in the physical, pain, and general domains of the SF36.Patients with longer IPAA time present worse results only in the general domain of SF36.

Table 1 .
Results of the comparison of early surgical complications between patients with UC and with FAP undergoing PCT with IPAA (n = 55).

Table 2 . Result of the comparison of the total of early complications
(n = 59) per patient and Clavien-Dindo classification between patients with FAP and with UC who underwent PCT with IPAA (n = 55).Alves Surgical results and quality of life of patients submitted to restorative proctocolectomy and ileal pouch-anal anastomosis

Table 3 .
Results of the comparison of late surgical complications between patients with UC and with FAP undergoing PCT with IPAA (n = 55).
1Pearson's exact chi-square test; ¥ excluded ileostomized patients.Pelvic complications occurred in 26 patients (47.3%) and corresponded to 44.0% of the total complications.There was no difference between diseases (UC and FAP) as for pelvic complications.IPAA failure occurred in 10.9% of patients, all with FAP.The causes of failure were two cases of IPAA anastomotic fistula, two of IPAA fistulas to other organs (one to the vagina and one to the urinary bladder), and one mesentery desmoid tumor resection with compromised vasculature of the reservoir.

Table 4 .
Result of the comparison of the ileoanal reservoir function and Quality of Life by sex and education.